Clinical pharmacology of antiplatelet drugs

Antiplatelet therapies target distinct pathways of platelet activation: thromboxane A2 synthesis, adenosine diphosphate-mediated signaling, integrin αIIbβ3 (GPIIb/IIIa), thrombin-mediated platelet activation via the PAR1 receptor and phosphodiesterases. Key clinical drug-drug interactions of antiplatelet agents involve acetylsalicylic acid - ibuprofen, clopidogrel - omeprazole, and morphine - oral P2Y12 inhibitors, all of which lead to an attenuated antiplatelet effect. Platelet function and genetic testing and the use of scores (ARC-HBR, PRECISE-DAPT, ESC ischemic risk definition) may contribute to a more tailored antiplatelet therapy. High on-treatment platelet reactivity presents a key problem in the acute management of ST-elevation myocardial infarction (STEMI). A treatment strategy involving early initiation of an intravenous antiplatelet agent may be able to bridge the gap of insufficient platelet inhibition in high ischemic risk patients with STEMI.